Male Mosquitoes Trigger Egg Production

Malaria-transmitting female Anopheles gambiae develop eggs upon mating as a result of a steroid hormone injected into them by males.

By Jef Akst | October 29, 2013

Anopheles gambiae mosquitoWIKIMEDIA, JAMES D. GATHANYFor a female Anopheles gambiae mosquito to develop and lay eggs, she must do two things: eat a blood meal, and mate. The latter, it turns out, can trigger egg development thanks to a steroid hormone passed from male to female in the gelatinous mating plug that he transfers at the end of copulation.

In a paper published today (October 29) in PLOS Biology, researchers from the Harvard School of Public Health and the University of Perugia in Italy detail the molecular pathway by which this hormone interacts with the female reproductive tract, identifying a receptor and an egg-development-triggering protein that mediate the male’s manipulation of the female’s physiology.

“[T]he paper provides insights into the complex biological cocktail that the male [mosquito] synthesizes to control the reproduction of the female he mates with,” mosquito physiologist Marc Klowden, a professor emeritus at the University of Idaho who was not involved in the research, told The Scientist in an e-mail. “It revolutionizes our understanding of the role of the mating plug and the components of the seminal fluid, which used to be referred to as the rather boring and nondescript ‘male accessory gland substance.’”

The study unravels “yet another important piece of the puzzle of the male-female reproductive interaction in Anopheles gambiae,” agreed Tania Dottorini, a bioinformatician who studies the species’ reproductive behavior at Imperial College London but was not involved in the study.

For the past five years, Flaminia Catteruccia, a malaria biologist affiliated with both Harvard and Perugia has been interrogating mosquito mating physiology, performing transcriptional and proteomics analyses to identify male and female factors important the reproductive behavior of this species. That female mosquitoes of this species only mate once is “a major limitation in their reproductive cycle,” she said. “If we can stop this single mating from happening or from producing fertile progeny, then we could really [interfere with] reproduction in these mosquitos, and so limit the number of mosquitoes that transmit malaria.”

In their search, Catteruccia and her colleagues identified a female protein they dubbed Mating-Induced Stimulator of Oogenesis (MISO), which the day following mating is expressed in the mosquito uterus (atrium) about a hundred-fold, compared with virgin females. Using RNA interference to knock down MISO, the researchers significantly reduced the numbers of eggs the females produced, pointing to the protein’s involvement in egg development.

“The identity and role of MISO completes another box in the flow chart that allows the mosquito to turn human blood into eggs,” Klowden wrote. “I think the paper will also have an influence on future discussions of the evolution of mating behavior and sexual selection.”

To further explore what was causing the massive upregulation of MISO in females post-mating, Catteruccia and her colleagues made “a bit of an educated guess,” and began investigating a previously identified male hormone called 20-hydroxy-ecdysone (20E). The researchers knew that male A. gambiae produce substantial 20E in their reproductive tissues, which is “not typical of mosquitos or insects in general,” Catteruccia noted. Furthermore, in other mosquito species where females produce much higher levels of 20E themselves and do not require mating to complete egg production, the hormone has been linked to the production of lipid transporters that accumulate lipids from blood meal into ovaries. “So we thought [20E] might be important for regulating egg development and the function of MISO” in A. gambiae, Catteruccia said.

Sure enough, 20E induces the expression of MISO via the ecdysone receptor (EcR) and interacts with MISO to trigger the development of eggs in female A. gambiae that have previously been fed a blood meal. Because females of this species do not produce enough 20E on their own to induce normal egg production, mating—and the receipt of 20E from the male—is required.

The findings, Dottorini noted, could inspire future reproduction-focused malaria control strategies. “Dissecting the mating-induced pathway of oogenesis in A. gambiae bears important implications for identifying novel targets for vector control in order to reduce mosquito populations in the wild either through chemical or genetic intervention,” she wrote in an e-mail.

Specifically, Catteruccia envisions two possibilities. “One of them is to target the male . . . so the male will be prevented from transferring this hormone, or transferring [it] at the same level.” It’s possible that a malaria-control strategy could then be developed based on the release of sterile males, she noted, though a few technical hurdles—such as ensuring that the engineered insects can outcompete the wild-type population and developing an efficient way to separate males from females before release—must be overcome.

Alternatively, Catteruccia suggested that targeting the molecular processes going on in the female, and combining that agent with current insecticides, might be a more practical and effective approach. “Adding some compounds that can make the females sterile or prevent the female from developing eggs would really slow down the spread of insecticide resistance,” she said. She referred to this souped-up class of insecticides as “smart insecticides,” and predicted that they “will be more effective and have a longer lifespan” than current malaria-control tools.

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What this paper suggests is that when a male mosquito copulates, it not only transfers sperms but along with that some steroid that serves to stimulate oogenesis.As an anology to vertebrates where oogenesis is to a large extent controlled by FSH, estrogen and progesterone in succession. In higher vertebrates copulation stimulates the female to cause ovulation and this happens through a neuroendocrine stimulation within the female.If the contention of the present paper is to be stressed upon, then the copulatory process the the mosquito does not serve to stimulate the production of steroid in the female that would stimulate egg production, and that oogenesis is dependent on exogenous supply of steroid from the male.It would be interesting to see what regulates the oviposition of eggs because oogensis and oviposition are two independent and spaced out events.